Evidence map›Paper›PMID 33872583›Full record

Trial reportThe American journal of medicine2021

Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial.

Jennifer Wilcox, Sarah M Skye, Brett Graham, Allyson Zabell, Xinmin S Li, Lin Li, Shamanthika Shelkay, Xiaoming Fu, Sarah Neale, Cathy O'Laughlin and 3 more

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The American journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 3 syntheses or guidelines pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Gut microbes · 2026
    Review
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  10. [Mechanisms of gutZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  11. Article
  12. Gut microbiota and atrial cardiomyopathy.Frontiers in cardiovascular medicine · 2025
    Review
  13. TrimethylamineCirculation. Heart failure · 2024
    Observational
  14. Article
  15. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Jennifer WilcoxDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute; Center for Microbiome and Human Health.
Sarah M SkyeDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Brett GrahamDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Allyson ZabellDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Xinmin S LiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute; Center for Microbiome and Human Health.
Lin LiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute; Center for Microbiome and Human Health.
Shamanthika ShelkayDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Xiaoming FuDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute; Center for Microbiome and Human Health.
Sarah NealeDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Cathy O'LaughlinDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Kimberly PetersonDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute.
Stanley L HazenDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute; Center for Microbiome and Human Health; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Ohio.
W H Wilson TangDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute; Center for Microbiome and Human Health; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Ohio. Electronic address: tangw@ccf.org.
HealthPartners · USCleveland Clinic · US

Funding

Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic diseaseP01HL147823 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MICHAEL ANDREW FISCHBACH · 2019 to 2026
$17.0M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
Diet, Gut Microbiota, and Heart FailureR01HL126827 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2016 to 2019
$3.1M
NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL126827
6 · The paper itself

Abstract

backgroundCholine is a dietary precursor to the gut microbial generation of the prothrombotic and proatherogenic metabolite trimethylamine-N-oxide (TMAO). Eggs are rich in choline, yet the impact of habitual egg consumption on TMAO levels and platelet function in human subjects remains unclear.

methodsHealthy volunteers (41% male, 81% Caucasian, median age 28 years) with normal renal function (estimated glomerular filtration rate >60) were recruited and assigned to 1 of 5 daily interventions for 4 weeks: 1) hardboiled eggs (n = 18); 2) choline bitartrate supplements (n = 20); 3) hardboiled eggs + choline bitartrate supplements (n = 16); 4) egg whites + choline bitartrate supplements (n = 18); 5) phosphatidylcholine supplements (n = 10). Fasting blood and urine samples were collected for quantification of TMAO, its precursors, and platelet aggregometry.

resultsParticipants' plasma TMAO levels increased significantly in all 3 intervention arms containing choline bitartrate (all P < .0001), but daily ingestion of 4 large eggs (P = .28) or phosphatidylcholine supplements (P = .27) failed to increase plasma TMAO levels. Platelet reactivity also significantly increased in the 3 intervention arms containing choline bitartrate (all P < .01), but not with eggs (P = .10) or phosphatidylcholine supplements (P = .79).

conclusionsDespite high choline content in egg yolks, healthy participants consuming 4 eggs daily showed no significant increase in TMAO or platelet reactivity. However, choline bitartrate supplements providing comparable total choline raised both TMAO and platelet reactivity, demonstrating that the form and source of dietary choline differentially contributes to systemic TMAO levels and platelet responsiveness.

Indexed as

CholinePhosphatidylcholinesAdultDietDrug MonitoringEgg WhiteEgg YolkFemaleHealthy VolunteersHumansLipotropic AgentsMaleMethylaminesPlatelet Function TestsTreatment OutcomeCholineLipotropic AgentsMethylaminesPhosphatidylcholinestrimethyloxamineCholineEggsTMAO

Identifiers

PMID33872583
PMCPMC8410632
OpenAlexW3154815312

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.